Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study.
OBJECTIVE
A phase II trial was conducted to determine the activity of prolonged oral etoposide in platinum-resistant and platinum-sensitive ovarian carcinoma.


METHODS
Platinum-resistant disease was defined as progression on platinum-based chemotherapy or recurrence within 6 months of completing therapy. The starting dose was 50 mg/m2/d (30 mg/m2/d for prior radiotherapy) for 21 days, every 28 days. A dose escalation to a maximum dose of 60 mg/m2/d was prescribed.


RESULTS
Of 99 patients entered, 97 were assessable for toxicity and 82 were assessable for response. Among 41 platinum-resistant patients a 26.8% response rate (7.3% complete response [CR] and 19.5% partial response [PR] rate) occurred. The median response duration was 4.3 months (range, 1.3 to 8.7), median progression-free interval (PFI) was 5.7 months (range, 0.8 to 30.8+), and median survival time was 10.8 months (range, 1.9 to 45.8). Twenty-five of 41 platinum-resistant patients had also previously received paclitaxel; of which eight (32%) responded. Among 41 platinum-sensitive patients, a 34.1% response rate (14.6% CR and 19.5% PR rate) occurred. The median response duration was 7.5 months (range, 1.9 to 15.2+), median PFI was 6.3+ months (range, 0.9 to 20.4), and median survival time was 16.5+ months (range, 0.9 to 34.8). Of 97 patients assessable for toxicity, grade 3 or 4 hematologic toxicity was common, with leukopenia occurring in 41.2% (grade 3, 29%; grade 4, 12%), neutropenia in 45.4% (grade 3, 20%; grade 4, 25%), thrombocytopenia in 9% (grade 3, 5%; grade 4, 4%), and anemia in 13.4%. Three treatment-related deaths occurred: two from neutropenic sepsis and one from thrombocytopenic bleeding after an overdose. One patient developed leukemia.


CONCLUSIONS
This regimen is active in platinum-resistant and platinum-sensitive ovarian carcinoma. Additionally, the regimen is active in paclitaxel-resistant ovarian carcinoma.
Rose
P G
PG
Department of Obstetrics and Gynecology, University Hospitals of Cleveland, Case Western Reserve University, OH, USA.
Blessing
J A
JA
Mayer
A R
AR
Homesley
H D
HD
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017671:Platinum Compounds / Q000627:therapeutic use
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D017671:Platinum Compounds; D005047:Etoposide